Correction of human nonsense mutation via adenine base editing for Duchenne muscular dystrophy treatment in mouse.

Duchenne muscular dystrophy (DMD) is the most prevalent herediatry disease in men, characterized by dystrophin deficiency, progressive muscle wasting, cardiac insufficiency, and premature mortality, with no effective therapeutic options. Here, we investigated whether adenine base editing can correct pathological nonsense point mutations leading to premature stop codons in the dystrophin gene. We identified 27 causative nonsense mutations in our DMD patient cohort.

The P286R mutation of DNA polymerase ε activates cancer-cell-intrinsic immunity and suppresses endometrial tumorigenesis via the cGAS-STING pathway.

Endometrial carcinoma (EC) is a prevalent gynecological tumor in women, and its treatment and prevention are significant global health concerns. The mutations in DNA polymerase ε (POLE) are recognized as key features of EC and may confer survival benefits in endometrial cancer patients undergoing anti-PD-1/PD-L1 therapy. However, the anti-tumor mechanism of POLE mutations remains largely elusive.

Multiple-Input-Multiple-Output Filtered Multitone Time Reversal Acoustic Communications Using Direct Adaptation-Based Turbo Equalization.

This paper proposes using direct adaptation (DA)-based turbo equalization in multiple-input-multiple-output (MIMO) filtered multitone (FMT) time reversal (TR) acoustic communications to jointly suppress noise, residual co-channel interference (CCI) and intersymbol interference (ISI) after the TR process. Soft information-based adaptive decision feedback equalization (ADFE) adjusted according to the recursive expected least squares (RELS) algorithm, including interference cancellation and decoding, is used to construct the DA-based turbo equalization. In the proposed method, soft information is exchanged between soft symbols with soft decisions of decoding iteratively, and interference suppression is proceeded successively and iteratively until the performance is stable.

Protein quality control and aggregation in the endoplasmic reticulum: From basic to bedside.

Endoplasmic reticulum (ER) is the largest membrane-bound compartment in all cells and functions as a key regulator in protein biosynthesis, lipid metabolism, and calcium balance. Mammalian endoplasmic reticulum has evolved with an orchestrated protein quality control system to handle defective proteins and ensure endoplasmic reticulum homeostasis. Nevertheless, the accumulation and aggregation of misfolded proteins in the endoplasmic reticulum may occur during pathological conditions.

CRISPR-Based Therapeutic Gene Editing for Duchenne Muscular Dystrophy: Advances, Challenges and Perspectives.

Duchenne muscular dystrophy (DMD) is a severe neuromuscular disease arising from loss-of-function mutations in the gene and characterized by progressive muscle degeneration, respiratory insufficiency, cardiac failure, and premature death by the age of thirty. Albeit DMD is one of the most common types of fatal genetic diseases, there is no curative treatment for this devastating disorder. In recent years, gene editing via the clustered regularly interspaced short palindromic repeats (CRISPR) system has paved a new path toward correcting pathological mutations at the genetic source, thus enabling the permanent restoration of dystrophin expression and function throughout the musculature.

Regulation of Embryonic Stem Cell Self-Renewal.

Embryonic stem cells (ESCs) are a type of cells capable of self-renewal and multi-directional differentiation. The self-renewal of ESCs is regulated by factors including signaling pathway proteins, transcription factors, epigenetic regulators, cytokines, and small molecular compounds. Similarly, non-coding RNAs, small RNAs, and microRNAs (miRNAs) also play an important role in the process.

Marine Application Evaluation of Monocular SLAM for Underwater Robots.

With the development of artificial intelligence technology, visual simultaneous localization and mapping (SLAM) has become a cheap and efficient localization method for underwater robots. However, there are many problems in underwater visual SLAM, such as more serious underwater imaging distortion, more underwater noise, and unclear details. In this paper, we study these two problems and chooses the ORB-SLAM2 algorithm as the method to obtain the motion trajectory of the underwater robot.

Comparative Analysis of the Therapeutic Effects of Amniotic Membrane and Umbilical Cord Derived Mesenchymal Stem Cells for the Treatment of Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM), one of the most common carbohydrate metabolism disorders, is characterized by chronic hyperglycemia and insulin resistance (IR), and has become an urgent global health challenge. Mesenchymal stem cells (MSCs) originating from perinatal tissues such as umbilical cord (UC) and amniotic membrane (AM) serve as ideal candidates for the treatment of T2DM due to their great advantages in terms of abundant source, proliferation capacity, immunomodulation and plasticity for insulin-producing cell differentiation. However, the optimally perinatal MSC source to treat T2DM remains elusive.

Time-delayed interactions on acoustically driven bubbly screens.

The influence of the compressibility effects is discussed, including the time delays on the dynamics of acoustically excited bubbly screens. In the linear regime, it is shown that the proposed model for the infinite bubbly screen recovers the results predicted by the effective medium theory (EMT) up to the second order without introducing any fitting parameter when the wavelength is large compared to the inter-bubble distance. However, the effect of boundaries on the finite bubbly screens is shown to lead to the appearance of multiple local resonances and characteristic periodic structures, which limit the applicability of the EMT.

Protein Aggregation in the ER: Calm behind the Storm.

As one of the largest organelles in eukaryotic cells, the endoplasmic reticulum (ER) plays a vital role in the synthesis, folding, and assembly of secretory and membrane proteins. To maintain its homeostasis, the ER is equipped with an elaborate network of protein folding chaperones and multiple quality control pathways whose cooperative actions safeguard the fidelity of protein biogenesis. However, due to genetic abnormalities, the error-prone nature of protein folding and assembly, and/or defects or limited capacities of the protein quality control systems, nascent proteins may become misfolded and fail to exit the ER.

How does CBCT reconstruction algorithm impact on deformably mapped targets and accumulated dose distributions?

Purpose: We performed quantitative analysis of differences in deformable image registration (DIR) and deformable dose accumulation (DDA) computed on CBCT datasets reconstructed using the standard (Feldkamp-Davis-Kress: FDK_CBCT) and a novel iterative (iterative_CBCT) CBCT reconstruction algorithms.

Methods: Both FDK_CBCT and iterative_CBCT images were reconstructed for 323 fractions of treatment for 10 prostate cancer patients. Planning CT images were deformably registered to each CBCT image data set.

Design and Experiments of a Portable Seabed Integrated Detection Sonar.

The integrated observation of seabed topography, sediment geomorphology and sub-bottom profile information is very important for seabed remote sensing and mapping. To improve the efficiency of seabed detection and meet the needs of portable development of detection equipment, we developed a portable seabed feature integrated detection sonar (PSIDS) with whcih a single sonar device can simultaneously detect the above three types of seabed information. The underwater transducer is mainly composed of the following three components: a parametric emission array as the sound source, a high frequency receiving linear array for multibeam echo signal collection, and a two-dimensional vector hydrophone for receiving the low-frequency sediment echo signal.

Mesenchymal Stem Cell-Based Therapy for Diabetes Mellitus: Enhancement Strategies and Future Perspectives.

Diabetes mellitus (DM), a chronic disorder of carbohydrate metabolism, is characterized by the unbridled hyperglycemia resulted from the impaired ability of the body to either produce or respond to insulin. As a cell-based regenerative therapy, mesenchymal stem cells (MSCs) hold immense potency for curing DM duo to their easy isolation, multi-differentiation potential, and immunomodulatory property. However, despite the promising efficacy in pre-clinical animal models, naive MSC administration fails to exhibit clinically satisfactory therapeutic outcomes, which varies greatly among individuals with DM.

Optimal subharmonic emission of stable bubble oscillations in a tube.

The subharmonic acoustic emission of a stable oscillating bubble inside a rigid tube is investigated by direct numerical simulation. The mechanisms of bubble-tube interaction on the acoustic wave emitted by the bubble are clarified. When the bubble is small compared to the tube diameter, a critical threshold for the pressure amplitude appears beyond the point which nonspherical effects become important and bubble breaks.

A simple model of bubble cluster dynamics in an acoustic field.

The dynamics of bubble clouds induced by ultrasound field are investigated in a regime where the cloud size is much smaller than the ultrasound wavelength. Two frequently used models describing the dynamics of individual bubbles inside a bubble cluster in an acoustic field are studied, one based on the homogeneity assumption, and the other based on the simultaneous motion assumption. A modified formula of the homogenization-based model is presented, and an inherent distinction in bubble-bubble interaction term is found in comparison to the simultaneous motion model.

Joint Time-Reversal Space-Time Block Coding and Adaptive Equalization for Filtered Multitone Underwater Acoustic Communications.

Underwater acoustic (UWA) sensor networks demand high-rate communications with high reliability between sensor nodes for massive data transmission. Filtered multitone (FMT) is an attractive multicarrier technique used in high-rate UWA communications, and can obviously shorten the span of intersymbol interference (ISI) with high spectral efficiency and low frequency offset sensitivity by dividing the communication band into several separated wide sub-bands without guard bands. The joint receive diversity and adaptive equalization scheme is often used as a general ISI suppression technique in FMT-UWA communications, but large receive array for high diversity gain has an adverse effect on the miniaturization of UWA sensor nodes.

Filtered Multitone Modulation Underwater Acoustic Communications Using Low-Complexity Channel-Estimation-Based MMSE Turbo Equalization.

Filtered multitone (FMT) modulation divides the communication band into several subbands to shorten the span of symbols affected by multipath in underwater acoustic (UWA) communications. However, there is still intersymbol interference (ISI) in each subband of FMT modulation degrading communication performance. Therefore, ISI suppression techniques must be applied to FMT modulation UWA communications.

Theoretical and experimental study on multibeam synthetic aperture sonar.

High-resolution imaging method is one of the researching focuses of underwater acoustic detection. Underwater small-target detection also requires detailed imaging technology. Multibeam echo sounders (MBESs) and synthetic aperture sonar (SAS) are the effective instruments widely researched to obtain underwater acoustic images.

Influence of bubble distributions on the propagation of linear waves in polydisperse bubbly liquids.

The influence of the spatial distributions of bubbles on the propagation of linear acoustic waves in polydisperse bubbly liquids is studied. Using the diagrammatic approach, the effective wavenumber, which includes both spatial information and higher orders of multiple scattering, is presented. The phase speed and attenuation coefficient of acoustic waves in bubbly liquids are calculated from the effective wavenumber.

On the improvement of CBCT image quality for soft tissue-based SRS localization.

Purpose: We explore the optimal cone-beam CT (CBCT) acquisition parameters to improve CBCT image quality to enhance intracranial stereotactic radiosurgery (SRS) localization and also assess the imaging dose levels associated with each imaging protocol.

Methods: Twenty-six CBCT acquisition protocols were generated on an Edge linear accelerator (Varian Medical Systems, Palo Alto, CA) with different x-ray tube current and potential settings, gantry rotation trajectories, and gantry rotation speeds. To assess image quality, images of the Catphan 504 phantom were analyzed to evaluate the following image quality metrics: uniformity, HU constancy, spatial resolution, low contrast detection, noise level, and contrast-to-noise ratio (CNR).

ATP Citrate Lyase: A New Player Linking Skeletal Muscle Metabolism and Epigenetics.

Intermediates generated in several metabolic processes are used to regulate transcription through covalent histone and DNA modifications. In Cell Reports, Das et al. show that acetyl-coenzyme A (acetyl-CoA) generated by ATP citrate lyase (ACL) is utilized to acetylate histone H3 at MyoD regulatory regions, resulting in increased MyoD expression and improved muscle regeneration after injury.

Stabilization of mouse haploid embryonic stem cells with combined kinase and signal modulation.

Mammalian haploid embryonic stem cells (haESCs) provide new possibilities for large-scale genetic screens because they bear only one copy of each chromosome. However, haESCs are prone to spontaneous diploidization through unknown mechanisms. Here, we report that a small molecule combination could restrain mouse haESCs from diploidization by impeding exit from naïve pluripotency and by shortening the S-G2/M phases.

Single-Cell Dynamic Analysis of Mitosis in Haploid Embryonic Stem Cells Shows the Prolonged Metaphase and Its Association with Self-diploidization.

The recent establishment of mammalian haploid embryonic stem cells (ESCs) provides new possibilities for genetic screening and for understanding genome evolution and function. However, the dynamics of mitosis in haploid ESCs is still unclear. Here, we report that the duration of mitosis in haploid ESCs, especially the metaphase, is significantly longer than that in diploid ESCs.

Characterization and evaluation of 2.5 MV electronic portal imaging for accurate localization of intra- and extracranial stereotactic radiosurgery.

2.5 MV electronic portal imaging, available on Varian TrueBeam machines, was characterized using various phantoms in this study. Its low-contrast detectability, spatial resolution, and contrast-to-noise ratio (CNR) were compared with those of conventional 6 MV and kV planar imaging.

Development of a deformable dosimetric phantom to verify dose accumulation algorithms for adaptive radiotherapy.

Adaptive radiotherapy may improve treatment outcomes for lung cancer patients. Because of the lack of an effective tool for quality assurance, this therapeutic modality is not yet accepted in clinic. The purpose of this study is to develop a deformable physical phantom for validation of dose accumulation algorithms in regions with heterogeneous mass.